PUBLICATION
Mutation of vsx genes in zebrafish highlights the robustness of the retinal specification network
- Authors
- Letelier, J., Buono, L., Almuedo-Castillo, M., Zang, J., Mounieres, C., González-Díaz, S., Polvillo, R., Sanabria-Reinoso, E., Corbacho, J., Sousa-Ortega, A., Diez Del Corral, R., Neuhauss, S.C.F., Martínez-Morales, J.R.
- ID
- ZDB-PUB-230526-30
- Date
- 2023
- Source
- eLIFE 12: (Journal)
- Registered Authors
- Martinez-Morales, Juan R., Neuhauss, Stephan
- Keywords
- CRISPR/Cas9, bipolar cells specification, developmental biology, evolutionary biology, medaka, medaka retina, neural retina network, vsx genes, zebrafish, zebrafish retina
- Datasets
- GEO:GSE189739, GEO:GSE189737, GEO:GSE189738
- MeSH Terms
-
- Humans
- Animals
- Eye Proteins/metabolism
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Homeodomain Proteins*/metabolism
- Transcription Factors/metabolism
- Mice
- Mutation
- Mammals/genetics
- Genes, Homeobox
- Retina/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 37227126 Full text @ Elife
Citation
Letelier, J., Buono, L., Almuedo-Castillo, M., Zang, J., Mounieres, C., González-Díaz, S., Polvillo, R., Sanabria-Reinoso, E., Corbacho, J., Sousa-Ortega, A., Diez Del Corral, R., Neuhauss, S.C.F., Martínez-Morales, J.R. (2023) Mutation of vsx genes in zebrafish highlights the robustness of the retinal specification network. eLIFE. 12:.
Abstract
Genetic studies in human and mice have established a dual role for Vsx genes in retina development: an early function in progenitors' specification, and a later requirement for bipolar-cells fate determination. Despite their conserved expression patterns, it is currently unclear to which extent Vsx functions are also conserved across vertebrates, as mutant models are available only in mammals. To gain insight into vsx function in teleosts, we have generated vsx1 and vsx2 CRISPR/Cas9 double knockouts (vsxKO) in zebrafish. Our electrophysiological and histological analyses indicate severe visual impairment and bipolar cells depletion in vsxKO larvae, with retinal precursors being rerouted toward photoreceptor or Müller glia fates. Surprisingly, neural retina is properly specified and maintained in mutant embryos, which do not display microphthalmia. We show that although important cis-regulatory remodelling occurs in vsxKO retinas during early specification, this has little impact at a transcriptomic level. Our observations point to genetic redundancy as an important mechanism sustaining the integrity of the retinal specification network, and to Vsx genes regulatory weight varying substantially among vertebrate species.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping